Biarnés Marc, Garrell-Salat Xavier, Gómez-Benlloch Alba, Guarro Mercè, Londoño Gabriel, López Elena, Ruiz Sergi, Vázquez Meritxell, Sararols Laura
OMIQ Research, Carrer de Pedro i Pons 1, 08195 Sant Cugat del Vallès, Spain.
Department of Ophthalmology, Hospital General de Granollers, Av. Francesc Ribas s/n, 08402 Granollers, Spain.
Biomedicines. 2023 May 26;11(6):1548. doi: 10.3390/biomedicines11061548.
Geographic atrophy (GA) secondary to age-related macular degeneration is a common cause of blindness worldwide. Given the recent approval of the first therapy for GA, pegcetacoplan, we critically appraise methodological aspects of the phase 3 clinical trials published so far in this disease in relation to their design, analysis and interpretation. We reviewed some of the key attributes of all phase 3 clinical trials in GA available in the main public registry of clinical trials as of 20 May 2023. The topics discussed included types of endpoints, eligibility criteria, -value and effect size, study power and sample size, the intention to treat principle, missing data, consistency of results, efficacy-safety balance and application of results. Five phase 3 clinical trials have reported results, either partially or completely: GATHER1, DERBY/OAKS, CHROMA/SPECTRI, SEATTLE and GATE. Although there are many similarities between these trials in terms of endpoints or broad eligibility criteria, they differ in several aspects (metric of the primary endpoint, sample size, type of adverse events, etc.) that can influence the results, which are discussed. Readers should understand key methodological aspects of clinical trials to improve their interpretation. On the other hand, authors should adhere to clinical trial reporting guidelines to communicate what was done and how it was done.
年龄相关性黄斑变性继发的地理性萎缩（GA）是全球范围内导致失明的常见原因。鉴于首个用于GA的疗法培西加可普坦（pegcetacoplan）最近已获批，我们严格评估了迄今为止发表的关于该疾病的3期临床试验在设计、分析和解读方面的方法学问题。我们回顾了截至2023年5月20日在主要公共临床试验注册库中可获取的所有GA的3期临床试验的一些关键属性。讨论的主题包括终点类型、纳入标准、P值和效应大小、研究效能和样本量、意向性分析原则、缺失数据、结果的一致性、疗效-安全性平衡以及结果的应用。五项3期临床试验已报告了部分或全部结果：GATHER1、DERBY/OAKS、CHROMA/SPECTRI、SEATTLE和GATE。尽管这些试验在终点或广泛的纳入标准方面有许多相似之处，但它们在几个可能影响结果的方面存在差异（主要终点的指标、样本量、不良事件类型等），对此进行了讨论。读者应了解临床试验的关键方法学问题以改进对结果的解读。另一方面，作者应遵循临床试验报告指南来传达所做的工作以及如何开展的工作。
